Abstract
PURPOSE: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), dupilumab vs placebo significantly reduced asthma exacerbation rates (AER) and improved pre-bronchodilator forced expiratory volume in 1 second (FEV(1)) in patients with uncontrolled, moderate-to-severe asthma, with greater effects in patients with elevated T2 biomarkers (≥150 eosinophils/µL or fractional exhaled nitric oxide [FeNO] ≥25 parts per billion). Overall safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed dupilumab efficacy in QUEST patients with T2 asthma with evidence of an allergic phenotype (baseline serum IgE ≥30 IU/mL and aeroallergen-specific IgE ≥0.35 IU/mL) by number of aeroallergen sensitizations: 1, 2, 3, or ≥4. Non-sensitized patients (serum total IgE <30 IU/mL without evidence of allergic phenotype) were also assessed. PATIENTS AND METHODS: Endpoints were annualized AER, change from baseline in pre-bronchodilator FEV(1) and asthma control (5-item Asthma Control Questionnaire [ACQ-5]), and FeNO and serum total IgE levels over the 52-week treatment period. RESULTS: In all subgroups by number of allergens sensitized, dupilumab vs placebo reduced AER by 35-67% and improved both pre-bronchodilator FEV(1) at Week 12 (least squares mean differences: 0.10-0.26 L across subgroups) and ACQ-5 score at Week 52 (-0.26 to -0.43). Dupilumab significantly reduced FeNO and total IgE levels at Week 52 compared with placebo. Similar results were observed in non-sensitized patients. CONCLUSION: Dupilumab improved clinical outcomes and reduced biomarker levels in patients with uncontrolled, moderate-to-severe T2 asthma irrespective of allergen sensitization status or number. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02414854.